This Research Project is a continuation of a long range plan to conduct clinical studies to test the hypothesis that improved local control shall result in decreased rates of metastatic disease and increased survival. Having established the feasibility of increasing tumor doses with 3DCRT techniques, we shall establish the maximum tolerable dose and to eventually test the basic hypothesis outlined above. Accordingly, we propose to continue our phase I dose-escalation clinical trial patients with stage T2-T3 carcinoma of the prostate and in stage T1-T4, N0-N2 non-small cell lung cancer (NSCLC) to determine the highest feasible radiation doses for these tumors. This will be facilitated by our recently developed programs of inverse planning to design intensity modulated beams and dynamic multileaf collimator treatment delivery. In addition, a phase II study in T1c-T2b intermediate risk prostate cancer will be initiated to obtain more definitive clinical data on the effects of enhanced doses on the rates of local tumor control and outcome. For the treatment of lung, we have modified our dose escalation protocol to incorporate radiobiological indices as input. Patients with T1-4, N0-2, N0 non-small-cell lung carcinoma will be accrued for dose escalation. A combination of prescription dose and fractional lung damage, calculated with a parallel architecture model, form the criteria to stratify patients in dose escalation. We also aim to construct a coherent strategy for the dose escalation that makes optimal use of the volume effect in conformal therapy. Our strategy is to continue to gather data on treatment complications, to use this and 3D dose data to develop/refine models, to extractmodel- independent information concerning the volume effect, and to use these insights in the design of future treatments. The new dose escalation protocol for lung is a direct result of the result of the advance in our understanding of the partial volume effect. Research proposed in Project IV, on the use of deep inspiration breath-hold for lung treatment and on the optimized field edge setting base on statistical uncertainty data, may provide improved treatment delivery for this clinical study in the later part of the next five year period.